The present proposal is for the continuation of an ongoing project designed to clarify the timing of the development of structural brain abnormalities previously found to be present in chronic schizophrenia, and to determine whether progressive brain morphological deterioration occurs in some patients. Eighty-seven patients who satisfy DSM-III-R criteria for schizophreniform disorder, schizoaffective disorder, of subchronic schizophrenia at their first hospital admission have been participating in a prospective longitudinal study of clinical, neuropsychological, and brain structural change over the first six years of illness. Fifty-two controls without any major psychiatric illness from the surrounding community have also been followed for comparison. Ventricular enlargement, subtle loss of normal cerebral asymmetries, reduced corpus callosal size, increased prevalence of a cavum septum pellucidum, and a generalized reduction in cortical grey matter were initially found in this group, while specific reductions of the size of temporal cortex or limbic structures were not found. A subgroup of 20 patients have completed the four year follow-up were found to have a significant decrease in cortical volume over time that was not specific to one region and not present in controls. At the end of the requested three year continuation of this project, all subjects will have completed six years of follow-up and the data will have been analyzed. These data will provide for or against progressive brain change in some cases of schizophrenia during the initial six years of illness and, if present, whether structural deteriorating over time is associated with clinical or cognitive deterioration. Results from this study will also aid in determining whether clinical outcome at six years can be predicted by the presence of brain structural anomalies present at the onset. Detailed systematically obtained records on this group of patients and controls will be maintained in order to provide a cohort for future more long-term follow-up investigations into the course of schizophrenia.